Sex-hormone-driven innate antibodies protect females and infants against EPEC infection.

Females have an overall advantage over males in resisting Gram-negative bacteremias, thus hinting at sexual dimorphism of immunity during infections. Here, through intravital microscopy, we observed a sex-biased difference in the capture of blood-borne bacteria by liver macrophages, a process that is critical for the clearance of systemic infections. Complement opsonization was indispensable for the capture of enteropathogenic Escherichia coli (EPEC) in male mice; however, a faster complement component 3-independent process involving abundant preexisting antibodies to EPEC was detected in female mice. These antibodies were elicited predominantly in female mice at puberty in response to estrogen regardless of microbiota-colonization conditions. Estrogen-driven antibodies were maternally transferrable to offspring and conferred protection during infancy. These antibodies were conserved in humans and recognized specialized oligosaccharides integrated into the bacterial lipopolysaccharide and capsule. Thus, an estrogen-driven, innate antibody-mediated immunological strategy conferred protection to females and their offspring.

"The Cost in the Individual": Longitudinal Burnout Prevalence Among Pediatric Emergency Physicians Through 9 Months of the COVID-19 Pandemic.

OBJECTIVES: Emergency medicine (EM) confers a high risk of burnout that may be exacerbated by the COVID-19 pandemic. We aimed to determine the longitudinal prevalence of burnout in pediatric EM (PEM) physicians/fellows working in tertiary PEM departments across Canada and its fluctuation during the pandemic. METHODS: A national mixed-methods survey using a validated 2-question proxy for burnout was distributed monthly through 9 months. The primary outcome was the trajectory in probability of burnout, which was examined as both emotional exhaustion (EE) and depersonalization (DP), EE alone, and DP alone. Secondary outcomes investigated burnout and its association with demographic variables. Quantitative data were analyzed using logistic regression for primary outcomes and subanalyses for secondary outcomes. Conventional content analysis was used to analyze qualitative data and generate themes. RESULTS: From February to October 2021, 92 of 98 respondents completed at least 1 survey, 78% completed at least 3 consecutive surveys, and 48% completed at least 6 consecutive surveys. Predicted probability of EE was bimodal with peaks in May (25%) and October (22%) 2021. Rates of DP alone or having both EE and DP were approximately 1% and stable over the study period. Mid-career physicians were at lower risk of EE (odds ratio, 0.02; 95% confidence interval, 0-0.22) compared with early-career physicians. Underlying drivers of burnout were multifaceted. CONCLUSIONS: Our study suggests that increased COVID-19 case burden was correlated with EE levels during the third and fourth waves of the pandemic. Emotional exhaustion was worsened by systemic factors, and interventions must target common themes of unsustainable workloads and overwhelming lack of control.

Metabolomics in pediatric lower respiratory tract infections and sepsis: a literature review.

Lower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality in children. The ability of healthcare providers to diagnose and prognose LRTIs in the pediatric population remains a challenge, as children can present with similar clinical features regardless of the underlying pathogen or ultimate severity. Metabolomics, the large-scale analysis of metabolites and metabolic pathways offers new tools and insights that may aid in diagnosing and predicting the outcomes of LRTIs in children. This review highlights the latest literature on the clinical utility of metabolomics in providing care for children with bronchiolitis, pneumonia, COVID-19, and sepsis. IMPACT: This article summarizes current metabolomics approaches to diagnosing and predicting the course of pediatric lower respiratory infections. This article highlights the limitations to current metabolomics research and highlights future directions for the field.

Willingness to Vaccinate Children against Influenza after the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: To determine factors associated with parents who plan to vaccinate their children against influenza next year, especially those who did not vaccinate against influenza last year using a global survey. STUDY DESIGN: A survey of caregivers accompanying their children aged 1-19 years old in 17 pediatric emergency departments in 6 countries at the peak of the coronavirus disease 2019 (COVID-19) pandemic. Anonymous online survey included caregiver and child demographic information, vaccination history and future intentions, and concern about the child and caregiver having COVID-19 at the time of emergency department visit. RESULTS: Of 2422 surveys, 1314 (54.2%) caregivers stated they plan to vaccinate their child against influenza next year, an increase of 15.8% from the previous year. Of 1459 caregivers who did not vaccinate their children last year, 418 (28.6%) plan to do so next year. Factors predicting willingness to change and vaccinate included child's up-to-date vaccination status (aOR 2.03, 95% CI 1.29-3.32, P = .003); caregivers' influenza vaccine history (aOR 3.26, 95% CI 2.41-4.40, P < .010), and level of concern their child had COVID-19 (aOR 1.09, 95% CI 1.01-1.17, P = .022). CONCLUSIONS: Changes in risk perception due to COVID-19, and previous vaccination, may serve to influence decision-making among caregivers regarding influenza vaccination in the coming season. To promote influenza vaccination among children, public health programs can leverage this information.

Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators.

OBJECTIVES: We aimed to demonstrate the potential of precision medicine to describe the inflammatory landscape present in children with suspected appendicitis. Our primary objective was to determine levels of seven inflammatory protein mediators previously associated with intra-abdominal inflammation (C-reactive protein-CRP, procalcitonin-PCT, interleukin-6 (IL), IL-8, IL-10, monocyte chemoattractant protein-1-MCP-1, and serum amyloid A-SAA) in a cohort of children with suspected appendicitis. Subsequently, using a multiplex proteomics approach, we examined an expansive array of novel candidate cytokine and chemokines within this population. METHODS: We performed a secondary analysis of targeted proteomics data from Alberta Sepsis Network studies. Plasma mediator levels, analyzed by Luminex multiplex assays, were evaluated in children aged 5-17 years with nonappendicitis abdominal pain (NAAP), acute appendicitis (AA), and nonappendicitis sepsis (NAS). We used multivariate regression analysis to evaluate the seven target proteins, followed by decision tree and heat mapping analyses for all proteins evaluated. RESULTS: 185 children were included: 83 with NAAP, 79 AA, and 23 NAS. Plasma levels of IL-6, CRP, MCP-1, PCT, and SAA were significantly different in children with AA compared to those with NAAP (p < 0.001). Expansive proteomic analysis demonstrated 6 patterns in inflammatory mediator profiles based on severity of illness. A decision tree incorporating the proteins CRP, ferritin, SAA, regulated on activation normal T-cell expressed and secreted (RANTES), monokine induced by gamma interferon (MIG), and PCT demonstrated excellent specificity (0.920) and negative predictive value (0.882) for children with appendicitis. CONCLUSIONS: Multiplex proteomic analyses described the inflammatory landscape of children presenting to the ED with suspected appendicitis. We have demonstrated the feasibility of this approach to identify potential novel candidate cytokines/chemokine patterns associated with a specific illness (appendicitis) amongst those with a broad ED presentation (abdominal pain). This approach can be modelled for future research initiatives in pediatric emergency medicine.

Test characteristics of common appendicitis scores with and without laboratory investigations: a prospective observational study.

BACKGROUND: Despite the poor independent test characteristics of the white blood cell count (WBC) and neutrophil count (NC) in identifying appendicitis, common clinical decision supports including the Pediatric Appendicitis Score (PAS) and Alvarado Score (AS), require the WBC and NC values. Moreover, blood tests cause discomfort/pain to children and require time for processing results. Scores based on clinical information alone may be of benefit in the pediatric population. The objective of our study was to determine the test characteristics of the PAS and the AS with and without laboratory investigations (mPAS, mAS respectively) as well as the Lintula Score. METHODS: A prospective cohort study of children aged 5-17 years presenting to a pediatric ED with suspected appendicitis. Clinical care of the patient was left to the managing physician. At risk for appendicitis was defined by PAS ≥6; AS ≥5; LS ≥16, as originally described; modified cutoffs were defined as mPAS ≥4; mAS ≥4. Appendicitis was defined as acute inflammation, rupture or abscess of the appendix on pathologic evaluation. Test characteristics for each of the 5 scores were calculated. RESULTS: Of the 180 eligible children, 102 (56.7 %) were female. The average age was 11.2 years (SD 3.1). Appendectomy was performed in 58 (32.2 %) of children, 55 (94.8 %) were positive. For the PAS and mPAS, sensitivity and negative predictive values were similar (80.0 %, 86.4 % vs 87.3 %, 85.1 % respectively). For the AS and mAS, sensitivity and negative predictive values were also similar (85.5 %, 87.1 % vs 83.6 %, 83.3 % respectively). Specificities in the PAS, mPAS, AS and mAS were low (56.0 %, 32.0 %, 43.2 %, 63.0 % respectively). Test characteristics of the LS were poor (59.3 %, 79.2 %, 55.2 %, 81.8 %). CONCLUSIONS: A modified Alvarado and PAS can be used to screen for children at low risk of appendicitis who may be carefully observed at home without the need for laboratory investigation. Translation to primary care settings should evaluate generalizability and determine impact on referral patterns.

Ondansetron Oral Dissolve Tab vs. Oral Solution in Children Presenting to the Emergency Department with Gastroenteritis.

BACKGROUND: Ondansetron is often used in the emergency department (ED) to promote oral rehydration in children with acute gastroenteritis (AGE), yet medication solutions administered orally may be poorly tolerated in this population. OBJECTIVES: We compared the tolerability of ondansetron oral dissolve tab (ODT) to oral solution (OS) in children presenting to the ED with AGE. METHODS: Using alternate-day controlled clinical trial design, children aged 3 months to 10 years received either ondansetron ODT or OS. Our primary outcome was early vomiting (within 15 min of drug administration). The secondary outcome was intravenous (i.v.) fluid administration. RESULTS: There were 462/534 eligible children who met study criteria. Demographics, severity, and duration of illness were similar between groups. Using intention-to-treat analysis, early vomiting occurred in 8/209 ODT vs. 19/253 OS children (3.8% vs. 7.5%; odds ratio [OR] 0.49; 95% confidence interval [CI] 0.18-1.21). Using as-treated analysis, 6/222 (2.7%) children receiving ODT experienced early vomiting, compared with 21/221 (9.5%) of the OS group (OR 0.26; 95% CI 0.09-0.70). The proportion of children discharged without i.v. fluids was not different (intention-to-treat: ODT = 91.4% (191/209), OS = 94.1% (238/253), OR 1.49, 95% CI 0.69-3.28; as-treated: ODT = 92.3% (205/222), OS = 93.2% (206/221), OR 0.88, 95% CI 0.40-1.93). CONCLUSIONS: Using a conservative intention-to-treat analysis, we found that children presenting to an ED with AGE did not have statistically less early vomiting with ondansetron ODT as compared with OS. However, our as-treated analysis demonstrates that children receiving ondansetron ODT experienced early vomiting approximately one-third as often as those receiving OS. The rate of i.v. fluid administration was no different between groups regardless of the type of analysis used.

Implementation of an Advanced Nursing Directive for Children With Right Lower Quadrant Pain: Identifying Those Requiring Further Investigation and Improving Flow Metrics.

OBJECTIVES: Advanced nursing directives (ANDs) empower nursing staff to provide advanced levels of care before physician assessment. The objectives of this study were (1) to determine whether an AND for right lower quadrant (RLQ) pain could identify children who required any further investigation to diagnose appendicitis and (2) to determine whether children meeting AND criteria had better emergency department (ED) flow metrics compared with those who did not meet the criteria. METHODS: Health records of children aged 3 to 17 years presenting to the ED with abdominal pain who were managed using the departmental AND for RLQ pain were reviewed. Primary outcomes included (1) the proportion of patients requiring further investigation to diagnose appendicitis and (2) the time interval from triage to blood draw. Secondary outcomes included additional ED flow metrics, perforation rate, and negative appendectomy rate. RESULTS: An AND was completed for 210 children. Those who met the AND criteria were more likely to undergo further investigation to rule out appendicitis than those who did not meet the criteria (92/137 [67.2%] vs 32/73 [43.8%]; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.40-4.90). Time to blood draw was significantly lower for those children meeting the AND criteria (74 vs 162 minutes, P < 0.001) as was time to hospital admission (271 vs 395 minutes, P = 0.008) and appendectomy (498 vs 602 minutes, P = 0.015). The negative appendectomy rate was 8.6% (5/58) for children meeting the AND criteria and 9.1% (2/22) for those not meeting the criteria (OR, 0.94; 95% CI, 0.14-10.67); the perforation rate was 29.3% (17/58) and 4.5% (1/22), respectively (OR, 8.17; 95% CI, 1.17-380.86). CONCLUSIONS: Children presenting to the ED with RLQ pain who meet the AND criteria are more likely to require further investigation to rule out appendicitis and have better department flow metrics than those who do not meet the criteria. Our results provide further evidence of the utility of ANDs in the ED.

Development of metabolic and inflammatory mediator biomarker phenotyping for early diagnosis and triage of pediatric sepsis.

INTRODUCTION: The first steps in goal-directed therapy for sepsis are early diagnosis followed by appropriate triage. These steps are usually left to the physician's judgment, as there is no accepted biomarker available. We aimed to determine biomarker phenotypes that differentiate children with sepsis who require intensive care from those who do not. METHODS: We conducted a prospective, observational nested cohort study at two pediatric intensive care units (PICUs) and one pediatric emergency department (ED). Children ages 2-17 years presenting to the PICU or ED with sepsis or presenting for procedural sedation to the ED were enrolled. We used the judgment of regional pediatric ED and PICU attending physicians as the standard to determine triage location (PICU or ED). We performed metabolic and inflammatory protein mediator profiling with serum and plasma samples, respectively, collected upon presentation, followed by multivariate statistical analysis. RESULTS: Ninety-four PICU sepsis, 81 ED sepsis, and 63 ED control patients were included. Metabolomic profiling revealed clear separation of groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.89, area under the receiver operating characteristic curve (AUROC) of 0.96 (standard deviation [SD] 0.01), and predictive ability (Q(2)) of 0.60. Protein mediator profiling also showed clear separation of the groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.78 and AUROC of 0.88 (SD 0.03). Combining metabolomic and protein mediator profiling improved the model (Q(2) =0.62), differentiating PICU sepsis from ED sepsis with accuracy of 0.87 and AUROC of 0.95 (SD 0.01). Separation of PICU sepsis or ED sepsis from ED controls was even more accurate. Prespecified age subgroups (2-5 years old and 6-17 years old) improved model accuracy minimally. Seventeen metabolites or protein mediators accounted for separation of PICU sepsis and ED sepsis with 95% confidence. CONCLUSIONS: In children ages 2-17 years, combining metabolomic and inflammatory protein mediator profiling early after presentation may differentiate children with sepsis requiring care in a PICU from children with or without sepsis safely cared for outside a PICU. This may aid in making triage decisions, particularly in an ED without pediatric expertise. This finding requires validation in an independent cohort.

Recognition and Management of Sepsis in Children: Practice Patterns in the Emergency Department.

BACKGROUND: Pediatric sepsis remains a leading cause of morbidity and mortality. Understanding current practice patterns and challenges is essential to inform future research and education strategies. OBJECTIVE: Our aim was to describe the practice patterns of pediatric emergency physicians (PEPs) in the recognition and management of sepsis in children and to identify perceived priorities for future research and education. METHODS: We conducted a cross-sectional, internet-based survey of members of the American Academy of Pediatrics, Section on Emergency Medicine and Pediatric Emergency Research Canada. The survey was internally derived, externally validated, and distributed using a modified Dillman methodology. Rank scores (RS) were calculated for responses using Likert-assigned frequency values. RESULTS: Tachycardia, mental-status changes, and abnormal temperature (RS = 83.7, 80.6, and 79.6) were the highest ranked clinical measures for diagnosing sepsis; white blood cell count, lactate, and band count (RS = 73.5, 70.9, and 69.1) were the highest ranked laboratory investigations. The resuscitation fluid of choice (85.5%) was normal saline. Dopamine was the first-line vasoactive medication (VAM) for cold (57.1%) and warm (42.2%) shock with epinephrine (18.5%) and norepinephrine (25.1%) as second-line VAMs (cold and warm, respectively). Steroid administration increased with complexity of presentation (all-comers 3.8%, VAM-resistant shock 54.5%, chronic steroid users 72.0%). Local ED-specific clinical pathways, national emergency department (ED)-specific guidelines, and identification of clinical biomarkers were described as future priorities. CONCLUSIONS: While practice variability exists among clinicians, PEPs continue to rely heavily on clinical metrics for recognizing sepsis. Improved recognition through clinical biomarkers and standardization of care were perceived as priorities. Our results provide a strong framework to guide future research and education strategies in pediatric sepsis.

Gene Expression Profiling in Pediatric Appendicitis.

Importance: Appendicitis is the most common indication for urgent surgery in the pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) and perforated appendicitis (PA) on presentation may help direct further diagnostic workup and appropriate therapy selection, including antibiotic choice and timing of surgery. Objective: To provide a mechanistic understanding of the differences in disease severity of appendicitis with the objective of developing improved diagnostics and treatments, specifically for the pediatric population. Design, Setting, and Participants: The Gene Expression Profiling of Pediatric Appendicitis (GEPPA) study was a single-center prospective exploratory diagnostic study with transcriptomic profiling of peripheral blood collected from a cohort of children aged 5 to 17 years with abdominal pain and suspected appendicitis between November 2016 and April 2017 at the Alberta Children's Hospital in Calgary, Alberta, Canada, with data analysis reported in August 2023. There was no patient follow-up in this study. Exposure: SA, PA, or nonappendicitis abdominal pain. Main Outcomes and Measures: Blood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics. Results: Seventy-one children (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) presenting to the emergency department with abdominal pain and suspected appendicitis were investigated using whole-blood transcriptomics. A central role for immune system pathways was revealed in PA, including a dampening of major innate interferon responses. Gene expression changes in patients with PA were consistent with downregulation of immune response and inflammation pathways and shared similarities with gene expression signatures derived from patients with sepsis, including the most severe sepsis endotypes. Despite the challenges in identifying early biomarkers of severe appendicitis, a 4-gene signature that was predictive of PA compared to SA, with an accuracy of 85.7% (95% CI, 72.8-94.1) was identified. Conclusions: This study found that PA was complicated by a dysregulated immune response. This finding should inform improved diagnostics of severity, early management strategies, and prevention of further postsurgical complications.

Comparison of Two Automated Targeted Metabolomics Programs to Manual Profiling by an Experienced Spectroscopist for 1H-NMR Spectra.

Automated programs that carry out targeted metabolite identification and quantification using proton nuclear magnetic resonance spectra can overcome time and cost barriers that limit metabolomics use. However, their performance needs to be comparable to that of an experienced spectroscopist. A previously analyzed pediatric sepsis data set of serum samples was used to compare results generated by the automated programs rDolphin and BATMAN with the results obtained by manual profiling for 58 identified metabolites. Metabolites were selected using Student's t-tests and evaluated with several performance metrics. The manual profiling results had the highest performance metrics values, especially for sensitivity (76.9%), area under the receiver operating characteristic curve (0.90), precision (62.5%), and testing accuracy based on a neural net (88.6%). All three approaches had high specificity values (77.7-86.7%). Manual profiling by an expert spectroscopist outperformed two open-source automated programs, indicating that further development is needed to achieve acceptable performance levels.

Should COVID-19 vaccines be mandated in schools? - an international caregiver perspective.

OBJECTIVES: Caregiver attitudes toward mandating COVID-19 vaccines for their children are poorly understood. We aimed to determine caregiver acceptability of COVID-19 vaccine mandates for schools/daycares and assess if opposition to mandates would result in removal of children from the educational system. STUDY DESIGN: Perform a cross-sectional, anonymous survey of adult caregivers with children ≤ 18 years presenting to 21 pediatric emergency departments in the United States, Canada, Israel, and Switzerland, November 1st through December 31st, 2021. The primary outcome was caregiver acceptance rates for school vaccine mandates, and the secondary outcomes included factors associated with mandate acceptance and caregiver intention to remove the child from school. RESULTS: Of 4,393 completed surveys, 37% of caregivers were opposed to any school vaccine mandate. Caregiver acceptance was lowest for daycare settings (33%) and increased as the child's level of education increased, college (55%). 26% of caregivers report a high likelihood (score of 8-10 on 0-10 scale) to remove their child from school if the vaccine became mandatory. Child safety was caregivers' greatest concern over vaccine mandates. A multivariable model demonstrated intent to vaccinate their child for COVID-19 (OR = 8.9, 95% CI 7.3 to 10.8; P < 0.001) and prior COVID-19 vaccination for the caregiver (OR = 3.8, 95% CI 3.0 to 4.9; P < 0.001) had the greatest odds of increasing mandate acceptance for any school level. CONCLUSIONS: Many caregivers are resistant to COVID-19 vaccine mandates for schools, and acceptance varies with school level. One-fourth of caregivers plan to remove their child from the educational system if vaccines become mandated.

Adherence of families to a group a streptococcal pharyngitis protocol used in a pediatric emergency department.

OBJECTIVES: In an effort to limit inappropriate antibiotic use for children with pharyngitis, our pediatric emergency department (PED) has implemented a strep throat protocol using preprinted prescriptions given to families pending pharyngeal swab results. We sought to determine the rate of adherence of families managed with this protocol and to identify whether clinical features are associated with adherence. METHODS: We conducted a prospective cohort study of children aged 2 to 17 years presented to the PED with suspected group A streptococcal (GAS) pharyngitis. Prescription-filling activity was tracked using a novel carbon-copy prescription and compared with throat swab result. Health records were reviewed for demographic and clinical information. Adherence was defined as prescriptions being filled after notification of a positive swab result and prescriptions not being filled when throat swab result was negative. RESULTS: Three hundred nine children were screened for GAS pharyngitis. One hundred swabs (32.4%) were positive for GAS pharyngitis, of which 15 prescriptions were filled before swab results. No record of prescription filling was found for 37 of the children with positive swab results. Only 9 families (4.3%) filled the prescription when the swab result was negative. Overall, 247 families (80.2%) were adherent to the protocol. Families of children aged 2 to 5 years were more likely to be adherent than those aged 13 to 17 years (odds ratio, 3.5; 95% confidence interval, 1.15-10.66). CONCLUSIONS: Most families are adherent to our GAS pharyngitis protocol. Very few families filled prescriptions when the swab result was negative. Age was the only factor influencing adherence. Our current GAS pharyngitis protocol is an effective management strategy for children presenting with pharyngitis to the PED.

Novel molecular biomarkers and diagnosis of acute appendicitis in children.

Reliable and efficient diagnosis of pediatric appendicitis is essential for the establishment of a clinical management plan and improvement of patient outcomes. Current strategies used to diagnose a child presenting with a suspected appendicitis include laboratory studies, clinical scores and diagnostic imaging. Although these modalities work in conjunction with each other, one optimal diagnostic strategy has yet to be agreed upon. The recent introduction of precision medicine techniques such as genomics, transcriptomics, proteomics and metabolomics has increased both the diagnostic sensitivity and specificity of appendicitis. Using these novel strategies, the integration of precision medicine into clinical practice via point-of-care technologies is a plausible future. These technologies would assist in the screening, diagnosis and prognosis of pediatric appendicitis.

Metabolomics and Inflammatory Mediator Profiling for the Differentiation of Life-Threatening and Non-Severe Appendicitis in the Pediatric Population.

While children with appendicitis often have excellent clinical outcomes, some develop life-threatening complications including sepsis and organ dysfunction requiring pediatric intensive care unit (PICU) support. Our study applied a metabolomics and inflammatory protein mediator (IPM) profiling approach to determine the bio-profiles of children who developed severe appendicitis compared with those that did not. We performed a prospective case-control study of children aged 0-17 years with a diagnosis of appendicitis. Cases had severe disease resulting in PICU admission. Primary controls had moderate appendicitis (perforation without PICU); secondary controls had mild appendicitis (non-perforated). Serum samples were analyzed using Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy and Gas Chromatography-Mass Spectrometry (GC-MS); IPM analysis was performed using plasma bead-based multiplex profiling. Comparisons were made using multivariate data statistical analysis. Fifty-three children were included (15 severe, 38 non-severe). Separation between severe and moderate appendicitis demonstrated excellent sensitivity and specificity (100%, 88%; 14 compounds), separation between severe and mild appendicitis also showed excellent sensitivity and specificity (91%, 90%; 16 compounds). Biomarker patterns derived from metabolomics and IPM profiling are capable of distinguishing children with severe appendicitis from those with less severe disease. These findings provide an important first step towards developing non-invasive diagnostic tools for clinicians in early identification of children who are at a high risk of developing severe appendicitis.

Caregiver Willingness to Vaccinate Their Children against COVID-19 after Adult Vaccine Approval.

Vaccines against COVID-19 are likely to be approved for children under 12 years in the near future. Understanding vaccine hesitancy in parents is essential for reaching herd immunity. A cross-sectional survey of caregivers in 12 emergency departments (ED) was undertaken in the U.S., Canada, and Israel. We compared reported willingness to vaccinate children against COVID-19 with an initial survey and post-adult COVID-19 vaccine approval. Multivariable logistic regression models were performed for all children and for those <12 years. A total of 1728 and 1041 surveys were completed in phases 1 and 2, respectively. Fewer caregivers planned to vaccinate against COVID-19 in phase 2 (64.5% and 59.7%, respectively; p = 0.002). The most significant positive predictor of willingness to vaccinate against COVID-19 was if the child was vaccinated per recommended local schedules. Fewer caregivers plan to vaccinate their children against COVID-19, despite vaccine approval for adults, compared to what was reported at the peak of the pandemic. Older caregivers who fully vaccinated their children were more likely to adopt vaccinating children. This study can inform target strategy design to implement adherence to a vaccination campaign.

PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial.

BACKGROUND/AIMS: Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock. METHODS: The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under "exception from informed consent" in the USA or "deferred consent" in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed. DISCUSSION: PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings. TRIAL REGISTRATION: PRoMPT BOLUS was first registered at ClinicalTrials.gov ( NCT04102371 ) on September 25, 2019. Enrollment started on August 25, 2020.

National COVID-19 vaccine program progress and parents' willingness to vaccinate their children.

Vaccinating children against COVID-19 is critical as a public health strategy in order to reach herd immunity and prevent illness among children and adults. The aim of the study was to identify correlation between willingness to vaccinate children under 12 years old, and vaccination rate for adult population in Canada, the United States, and Israel. This was a secondary analysis of a cross-sectional survey study (COVID-19 Parental Attitude Study) of parents of children 12 years and younger presenting to 12 pediatric emergency departments (EDs). Parental reports of willingness to vaccinate against COVID-19 when vaccines for children will be approved was correlated to country-specific rate of vaccination during December 2020-March 2021, obtained from ourworldindata.org. Logistic regression models were fit with covariates for week and the corresponding vaccine rate. A total of 720 surveys were analyzed. In Canada, administering mostly first dose to the adult population, willingness to vaccinate children was trending downward (correlation = -0.28), in the United States, it was trending upwards (correlation = 0.21) and in Israel, initially significant increase with decline shortly thereafter (correlation = 0.06). Odds of willingness to vaccinate in Canada, the United States, and Israel was OR = 0.82, 95% CI = 0.63-1.07, OR = 1.24, 95% CI = 0.99-1.56, and OR = 1.03, 95% CI = 0.95-1.12, respectively. A robust population-based vaccination program as in Israel, and to a lesser degree the United States, led to increasing willingness by parents to vaccinate their children younger than 12 years against COVID-19. In Canada, slow rate of vaccination of the adult population was associated with lower willingness to vaccinate children.

Caregiver-reported delay in presentation to pediatric emergency departments for fear of contracting COVID-19: a multi-national cross-sectional study.

OBJECTIVE: To determine if caregivers of children presenting to pediatric emergency departments (EDs) during the COVID-19 pandemic are delaying presenting to care for fear of contracting COVID-19. METHODS: This was a pre-planned secondary analysis of a cross-sectional survey study of caregivers accompanying their children aged 0-19 years to 16 pediatric EDs in 5 countries from May to June 2020. An anonymous online survey, completed by caregivers via RedCAP, included caregiver and child demographics, presenting complaints, if they delayed presentation and whether symptoms worsened during this interval, as well as caregiver concern about the child or caregiver having COVID-19 at the time of ED visit. RESULTS: Of 1543 caregivers completing the survey, 287 (18.6%) reported a delay in seeking ED care due to concerns of contracting COVID-19 in the hospital. Of those, 124 (43.2%) stated their child's symptoms worsened during the waiting interval. Caregiver relationship to child [mother] (OR 1.85, 95% CI 1.27-2.76), presence of chronic illness in child (OR 1.78. 95% CI 1.14-2.79), younger age of caregiver (OR 0.965, 95% CI 0.943-0.986), and caregiver concerns about lost work during the pandemic (OR 1.08, 95% CI 1.04-1.12) were independently associated with a COVID-19-related delayed presentation in multivariable regression analysis. CONCLUSIONS: Almost one in five caregivers reported delaying ED presentation for their ill or injured child specifically due to fear of contracting COVID-19 while in hospital, with mothers, younger caregivers, caregivers of children with chronic illness, and those concerned about lost work more likely to report delaying ED presentation.

RéSUMé: OBJECTIF: Déterminer si les aidants des enfants qui se présentent aux services d'urgence pédiatriques (SU) pendant la pandémie de COVID-19 retardent leur présentation pour prendre soin d'eux par crainte de contracter la COVID-19. MéTHODES: Il s'agissait d'une analyze secondaire planifiée à l'avance d'une étude d'enquête transversale auprès des soignants accompagnant leurs enfants âgés de 0 à 19 ans dans 16 urgences pédiatriques de 5 pays entre mai et juin 2020. Une enquête anonyme en ligne, remplie par les soignants via RedCAP, comprenait les données démographiques du soignant et de l'enfant, les plaintes présentées, s'ils ont retardé la présentation et si les symptômes se sont aggravés pendant cet intervalle, ainsi que l'inquiétude du soignant quant à la présence de COVID-19 chez l'enfant ou le soignant au moment de la visite aux urgences. RéSULTATS: Sur les 1 543 soignants ayant répondu à l'enquête, 287 (18.6 %) ont déclaré avoir retardé le recours aux urgences par crainte de contracter le COVID-19 à l'hôpital. Parmi eux, 124 (43.2%) ont déclaré que les symptômes de leur enfant s'étaient aggravés pendant l'intervalle d'attente. Dans l'analyse de régression multivariable, le lien entre la personne qui s'occupe de l'enfant et la mère (OR 1.85, IC95 % 1.27­2.76), la présence d'une maladie chronique chez l'enfant (OR 1.78, IC95 % 1.14-2.79), le jeune âge de la personne qui s'occupe de l'enfant (OR 0.965, IC95 % 0.943-0.986) et les préoccupations de la personne qui s'occupe de l'enfant concernant la perte de travail pendant la pandémie (OR 1.08, IC95 % 1.04­1.12) ont été associés de manière indépendante à une présentation tardive. CONCLUSIONS: Près d'un soignant sur cinq a déclaré avoir retardé la présentation aux urgences de son enfant malade ou blessé par crainte de contracter le COVID-19 pendant son séjour à l'hôpital, avec les mères, les jeunes aidants, les soignants d'enfants souffrant de maladies chroniques et les personnes préoccupées par la perte de travail sont plus susceptibles de retarder la présentation aux urgences.